- Understanding the impact of halogen functional group (Br, Cl, F, OH) in amprenavir ligand of the HIV protease. [Journal Article]J Biomol Struct Dyn. 2023 Jan 16 [Online ahead of print]JB
- We focused our attention towards the most dreadful disease that threatens the mankind of 20th century - Acquired immunodeficiency syndrome (AIDS), caused through the human immunodeficiency virus (HIV) and a sexually transmitted infection (STI). In this study, our foremost interest was to identify the potency and stability of HIV ligand- Amprenavir (APV) and its modelled functional group (Br, Cl, …
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- In-vitro dynamic dissolution/bioconversion/permeation of fosamprenavir using a novel tool with an artificial biomimetic permeation barrier and microdialysis-sampling. [Journal Article]Eur J Pharm Sci. 2023 Feb 01; 181:106366.EJ
- Fosamprenavir is a phosphate ester prodrug that, upon dissolution, is cleaved to the poorly soluble yet readily absorbable parent drug amprenavir. In this study, a novel cell-free in vitro setup with quasi-continuous monitoring of the dynamic dissolution/bio-conversion/permeation of fosamprenavir was designed and tested. It consists of side-by-side diffusion cells, where the donor and acceptor co…
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- Decoding drug resistant mechanism of V32I, I50V and I84V mutations of HIV-1 protease on amprenavir binding by using molecular dynamics simulations and MM-GBSA calculations. [Journal Article]
- Mutations V32I, I50V and I84V in the HIV-1 protease (PR) induce drug resistance towards drug amprenavir (APV). Multiple short molecular dynamics (MSMD) simulations and molecular mechanics generalized Born surface area (MM-GBSA) method were utilized to investigate drug-resistant mechanism of V32I, I50V and I84V towards APV. Dynamic information arising from MSMD simulations suggest that V32I, I50V …
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- Interactions of Antiretroviral Drugs with Food, Beverages, Dietary Supplements, and Alcohol: A Systematic Review and Meta-analyses. [Review]
- Multiple factors may affect combined antiretroviral therapy (cART). We investigated the impact of food, beverages, dietary supplements, and alcohol on the pharmacokinetic and pharmacodynamic parameters of 33 antiretroviral drugs. Systematic review in adherence to PRISMA guidelines was performed, with 109 reports of 120 studies included. For each drug, meta-analyses or qualitative analyses were co…
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- Discovery of Novel HIV Protease Inhibitors Using Modern Computational Techniques. [Journal Article]
- The human immunodeficiency virus type 1 (HIV-1) has continued to be a global concern. With the new HIV incidence, the emergence of multi-drug resistance and the untoward side effects of currently used anti-HIV drugs, there is an urgent need to discover more efficient anti-HIV drugs. Modern computational tools have played vital roles in facilitating the drug discovery process. This research focuse…
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- Oral and Inhaled Fosamprenavir Reverses Pepsin-Induced Damage in a Laryngopharyngeal Reflux Mouse Model. [Journal Article]
- CONCLUSIONS: Fosamprenavir and darunavir, FDA-approved therapies for HIV/AIDS, bind and inhibit pepsin, abrogating pepsin-mediated laryngeal damage in a laryngopharyngeal reflux mouse model. These drugs target a foreign virus, making them ideal to repurpose. Reformulation for local inhaled delivery could further improve outcomes and limit side effects.
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- In silico analysis of SARS-CoV-2 proteins as targets for clinically available drugs. [Journal Article]
- The ongoing pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires treatments with rapid clinical translatability. Here we develop a multi-target and multi-ligand virtual screening method to identify FDA-approved drugs with potential activity against SARS-CoV-2 at traditional and understudied viral targets. 1,268 FDA-approved small molecule drugs were docked to 4…
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- Pharmacokinetic Outcomes of the Interactions of Antiretroviral Agents with Food and Supplements: A Systematic Review and Meta-Analysis. [Review]
- Because pharmacokinetic changes in antiretroviral drugs (ARV), due to their concurrent administration with food or nutritional products, have become a clinical challenge, it is necessary to monitor the therapeutic efficacy of ARV in people living with the human immunodeficiency virus (PLWH). A systematic review and meta-analysis were conducted to clarify the pharmacokinetic outcomes of the intera…
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- Novel Real-Time Library Search Driven Data Acquisition Strategy for Identification and Characterization of Metabolites. [Journal Article]Anal Chem. 2022 03 08; 94(9):3749-3755.AC
- Structural characterization of novel metabolites in drug discovery or metabolomics is one of the most challenging tasks. Multilevel fragmentation (MSn) based approaches combined with various dissociation modes are frequently utilized for facilitating structure assignment of unknown compounds. As each of the MS precursors undergoes MSn, the instrument cycle time can limit the total number of precu…
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- Fluorine Modifications Contribute to Potent Antiviral Activity against Highly Drug-Resistant HIV-1 and Favorable Blood-Brain Barrier Penetration Property of Novel Central Nervous System-Targeting HIV-1 Protease Inhibitors In Vitro. [Journal Article]
- To date, there are no specific treatment regimens for HIV-1-related central nervous system (CNS) complications, such as HIV-1-associated neurocognitive disorders (HAND). Here, we report that two newly generated CNS-targeting HIV-1 protease (PR) inhibitors (PIs), GRL-08513 and GRL-08613, which have a P1-3,5-bis-fluorophenyl or P1-para-monofluorophenyl ring and P2-tetrahydropyrano-tetrahydrofuran (…
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- Isolation of MDCK cells with low expression of mdr1 gene and their use in membrane permeability screening. [Journal Article]Acta Pharm. 2022 Jun 01; 72(2):275-288.AP
- The Madin-Darby canine kidney (MDCK) cell line is frequently used for permeability screening in drug discovery. It contains endogenous transporters, most prominently canine multidrug resistance P-glycoprotein (Mdr1), which can interfere with studies of P-glycoprotein substrate assessment and permeability measurements. Because MDCK wild type (WT) is genetically heterogeneous, an isolation procedur…
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- Repurposing drug molecule against SARS-Cov-2 (COVID-19) through molecular docking and dynamics: a quick approach to pick FDA-approved drugs. [Journal Article]
- A novel coronavirus known as severe acute respiratory syndrome is rapidly spreading worldwide. The international health authorities are putting all their efforts on quick diagnosis and placing the patients in quarantine. Although different vaccines have come for quick use as prophylactics, drug repurposing seems to be of paramount importance because of inefficient therapeutic options and clinical…
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- A New, Rapid and Simple RP-HPLC Method for Stability Quantification of a Protease Inhibitor in Tablets. [Journal Article]J Chromatogr Sci. 2022 Sep 03; 60(7):671-677.JC
- Fosamprenavir calcium is a protease inhibitor widely used in the treatment and prevention of human immunodeficiency virus and acquired immunodeficiency syndrome. This protease inhibitor serves as a prodrug of amprenavir, offering better oral bioavailability. Although this drug was approved by the FDA in 2003, there are few methods established for quantifying the stability for quality control anal…
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- Revertant mutation V48G alters conformational dynamics of highly drug resistant HIV protease PRS17. [Journal Article]
- Drug resistance is a serious problem for controlling the HIV/AIDS pandemic. Current antiviral drugs show several orders of magnitude worse inhibition of highly resistant clinical variant PRS17 of HIV-1 protease compared with wild-type protease. We have analyzed the effects of a common resistance mutation G48V in the flexible flaps of the protease by assessing the revertant PRS17V48G for changes i…
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- Predicted antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir can potentially bind to neutralize SARS-CoV-2 conserved proteins. [Journal Article]
- CONCLUSIONS: Repurposing of the antiviral drugs Darunavir, Amprenavir, Rimantadine and Saquinavir to treat COVID-19 patients could be useful that can potentially prevent human mortality.
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- Insights into effect of the Asp25/Asp25' protonation states on binding of inhibitors Amprenavir and MKP97 to HIV-1 protease using molecular dynamics simulations and MM-GBSA calculations. [Journal Article]SAR QSAR Environ Res. 2021 Aug; 32(8):615-641.SQ
- The protonation states of two aspartic acids in the catalytic strands of HIV-1 protease (PR) remarkably affect bindings of inhibitors to PR. It is requisite for the design of potent inhibitors towards PR to investigate the influences of Asp25/Asp25' protonated states on dynamics behaviour of PR and binding mechanism of inhibitors to PR. In this work, molecular dynamics (MD) simulations, MM-GBSA m…
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- Novel HIV PR inhibitors with C4-substituted bis-THF and bis-fluoro-benzyl target the two active site mutations of highly drug resistant mutant PRS17. [Journal Article]
- The emergence of multidrug resistant (MDR) HIV strains severely reduces the effectiveness of antiretroviral therapy. Clinical inhibitor darunavir (1) has picomolar binding affinity for HIV-1 protease (PR), however, drug resistant variants like PRS17 show poor inhibition by 1, despite the presence of only two mutated residues in the inhibitor-binding site. Antiviral inhibitors that target MDR prot…
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- Biomedical Text Link Prediction for Drug Discovery: A Case Study with COVID-19. [Journal Article]
- Link prediction in artificial intelligence is used to identify missing links or derive future relationships that can occur in complex networks. A link prediction model was developed using the complex heterogeneous biomedical knowledge graph, SemNet, to predict missing links in biomedical literature for drug discovery. A web application visualized knowledge graph embeddings and link prediction res…
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- Docking Study on Anti-HIV-1 Activity of Secondary Metabolites from Zingiberaceae Plants. [Journal Article]
- CONCLUSIONS: The docking molecular study has identified the possible potential compounds from Zingiberaceae plants that might be used for anti-HIV-1 treatment. So, this study suggested further isolation and purification of the predicted compounds.
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- Identification of potential antivirals against SARS-CoV-2 using virtual screening method. [Journal Article]
- SARS-CoV-2 has triggered a major epidemic among people around the world, and it is the newest in the sequence to become prevalent among other infectious diseases. The drug repurposing concept has been utilized effectively for numerous viral infections. Considering the situation and the urgency, the idea of drug repurposing for coronavirus infection (COVID-19) is also being studied. The molecular …
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- In-silico drug repurposing study: Amprenavir, enalaprilat, and plerixafor, potential drugs for destabilizing the SARS-CoV-2 S-protein-angiotensin-converting enzyme 2 complex. [Journal Article]
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that leads to coronavirus disease (COVID-19) has put public health at risk in 2020. The spike protein (SP) in SARS-CoV-2 is primarily responsible for the attachment and entry of the virus into the cell, which binds to the angiotensin-converting enzyme 2 (ACE2). Owing to the lack of an effective therapy, drug repositioning is an opportun…
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- The HIV - 1 protease inhibitor Amprenavir targets Leishmania donovani topoisomerase I and induces oxidative stress-mediated programmed cell death. [Journal Article]Parasitol Int. 2021 Jun; 82:102287.PI
- The global prevalence of HIV is a major challenge for the control of visceral leishmaniasis. Although the effectiveness and usefulness of amprenavir (APV) are well studied in anti-retroviral regimens, very little is known on HIV/VL-co-infected patients. In the present study, we report for the first time the protective efficacy of APV against visceral leishmaniasis by inhibition of DNA Topoisomera…
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- Evaluation of the Binding Affinity of Anti-Viral Drugs against Main Protease of SARS-CoV-2 Through a Molecular Docking Study. [Journal Article]
- CONCLUSIONS: In conclusion, protease inhibitors may be effective potential antiviral agents against Mpro to combat SARS-CoV-2.
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- Repurposing existing drugs for the treatment of COVID-19/SARS-CoV-2 infection: A review describing drug mechanisms of action. [Review]
- The outbreak of a novel coronavirus (SARS-CoV-2) has caused a major public health concern across the globe. SARS-CoV-2 is the seventh coronavirus that is known to cause human disease. As of September 2020, SARS-CoV-2 has been reported in 213 countries and more than 31 million cases have been confirmed, with an estimated mortality rate of ∼3%. Unfortunately, a drug or vaccine is yet to be discover…
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- Repurposing therapeutics for COVID-19: Rapid prediction of commercially available drugs through machine learning and docking. [Journal Article]
- CONCLUSIONS: Our study can help clinical scientists in being more selective in identifying and testing the therapeutic agents for COVID-19 treatment. The ML based approach for drug discovery as reported here can be a futuristic smart drug designing strategy for community applications.
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- Computational Evaluation of the Inhibition Efficacies of HIV Antivirals on SARS-CoV-2 (COVID-19) Protease and Identification of 3D Pharmacophore and Hit Compounds. [Journal Article]
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel coronavirus behind the fast-spreading coronavirus disease 2019 (COVID-19). Pharmaceutical researchers are currently researching medications or preventive vaccines that may be used to treat and combat the spread of COVID-19. Health practitioners all over the world are treating patients with currently available antiviral drug…
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- A Simplified Quantitative Real-Time PCR Assay for Monitoring SARS-CoV-2 Growth in Cell Culture. [Journal Article]
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions within just a few months, causing severe respiratory disease and mortality. Assays to monitor SARS-CoV-2 growth in vitro depend on time-consuming and costly RNA extraction steps, hampering progress in basic research and drug development efforts. Here, we developed a simplified quantitative real-time PCR assay that …
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- Destabilizing the structural integrity of COVID-19 by caulerpin and its derivatives along with some antiviral drugs: An in silico approaches for a combination therapy. [Journal Article]
- Presently, the SARS-CoV-2 (COVID-19) pandemic has been spreading throughout the world. Some drugs such as lopinavir, simeprevir, hydroxychloroquine, chloroquine, and amprenavir have been recommended for COVID-19 treatment by some researchers, but these drugs were not effective enough against this virus. This study based on in silico approaches was aimed to increase the anti-COVID-19 activities of…
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- Development of multipurpose recombinant reporter bovine leukemia virus. [Journal Article]
- Bovine leukemia virus (BLV) is a global problem that results in significant economic losses to the livestock industry. We developed three virus strains by inserting the HiBiT reporter tag from NanoLuc luciferase (NLuc) into limited sites within BLV molecular clones. Initial analysis for site selection of the tag insertion revealed a permissible site immediately downstream of the viral envelope ge…
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- A facile Q-RT-PCR assay for monitoring SARS-CoV-2 growth in cell culture. [Preprint]
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the ongoing COVID-19 pandemic, has infected millions within just a few months and is continuing to spread around the globe causing immense respiratory disease and mortality. Assays to monitor SARS-CoV-2 growth depend on time-consuming and costly RNA extraction steps, hampering progress in basic research and dru…
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